The Many Facets of Therapy Resistance and Tumor Recurrence in Glioblastoma.
The Many Facets of Therapy Resistance and Tumor Recurrence in Glioblastoma.
复制标题
DOI：
10.3390/cells10030484
复制
发表时间：
2021-02-24
期刊：
影响因子：
6
通讯作者：
Cheng SY
中科院分区：
文献类型：
--
作者：
Goenka A;Tiek D;Song X;Huang T;Hu B;Cheng SY
胶质母细胞瘤（GBM）是原发性脑癌中最致命的类型。采用化疗和放疗的标准治疗方法可适度提高患者的总体生存率；然而，由于治疗抗性以及对靶向治疗缺乏反应，复发不可避免。GBM的治疗抗性归因于若干外在和内在因素，这些因素影响肿瘤演变和生理的动态过程，从而带来临床挑战。肿瘤内在因素，如肿瘤异质性、超突变、代谢组学改变以及肿瘤激活的可变剪接通路，改变了肿瘤的状况，促使治疗失败和肿瘤进展。此外，肿瘤外在因素，如缺氧和免疫抑制性肿瘤微环境（TME）是GBM免疫治疗失败的主要原因。在免疫治疗在其他癌症中取得成功的情况下，GBM已成为抗性的典型，因此当前的工作重点不仅在于减轻免疫耐受性，还在于规避由肿瘤间和肿瘤内异质性导致的肿瘤细胞对治疗的逃逸机制。在此，我们综述了GBM中由不断演变的肿瘤动态以及复杂的TME所导致的各种治疗抗性机制，这些机制共同导致了GBM的恶性程度和治疗失败；试图理解并确定针对复发性GBM的有效治疗方法。
Glioblastoma (GBM) is the most lethal type of primary brain cancer. Standard care using chemo- and radio-therapy modestly increases the overall survival of patients; however, recurrence is inevitable, due to treatment resistance and lack of response to targeted therapies. GBM therapy resistance has been attributed to several extrinsic and intrinsic factors which affect the dynamics of tumor evolution and physiology thus creating clinical challenges. Tumor-intrinsic factors such as tumor heterogeneity, hypermutation, altered metabolomics and oncologically activated alternative splicing pathways change the tumor landscape to facilitate therapy failure and tumor progression. Moreover, tumor-extrinsic factors such as hypoxia and an immune-suppressive tumor microenvironment (TME) are the chief causes of immunotherapy failure in GBM. Amid the success of immunotherapy in other cancers, GBM has occurred as a model of resistance, thus focusing current efforts on not only alleviating the immunotolerance but also evading the escape mechanisms of tumor cells to therapy, caused by inter- and intra-tumoral heterogeneity. Here we review the various mechanisms of therapy resistance in GBM, caused by the continuously evolving tumor dynamics as well as the complex TME, which cumulatively contribute to GBM malignancy and therapy failure; in an attempt to understand and identify effective therapies for recurrent GBM.
登录
查看更多内容
影响因子：
29
作者：
Babic I;Anderson ES;Tanaka K;Guo D;Masui K;Li B;Zhu S;Gu Y;Villa GR;Akhavan D;Nathanson D;Gini B;Mareninov S;Li R;Camacho CE;Kurdistani SK;Eskin A;Nelson SF;Yong WH;Cavenee WK;Cloughesy TF;Christofk HR;Black DL;Mischel PS
通讯作者：
Mischel PS
影响因子：
5.2
作者：
Caragher S;Miska J;Shireman J;Park CH;Muroski M;Lesniak MS;Ahmed AU
通讯作者：
Ahmed AU
DOI：
10.1038/nrm.2017.27
发表时间：
2017-07
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Baralle FE;Giudice J
通讯作者：
Giudice J
影响因子：
7.3
作者：
Chen Z;Hambardzumyan D
通讯作者：
Hambardzumyan D
影响因子：
56.9
作者：
Bai, Rui;Wan, Ruixue;Shi, Yigong
通讯作者：
Shi, Yigong